Luiza Rusu

By Luiza Rusu and Richard D. Minshall

The main function of von Willebrand factor (vWF) is to initiate platelet adhesion upon vascular injury. The hallmark of acute and chronical inflammation is the widespread activation of endothelial cells which provokes excessive vWF secretion from the endothelial cell storage pool. The level of vWF in blood not only reflects the state of endothelial activation early on in the pathogenesis, but also predicts disease outcome. Elevation in the blood level of vWF occurs either by pathologic increase in the rate of basal vWF secretion or by increased evoked vWF release from dysfunctional/activated endothelial cells (ECs). The increase in plasma vWF is predictive of prothrombotic complications and multi-organ system failure associated with reduced survival in the context of severe inflammatory response syndrome, type II diabetes mellitus, stroke and other inflammatory cardiovascular disease states. This chapter focuses on the role of high circulating vWF levels in thrombotic and inflammatory disease while paying attention to the emerging vWF-related drug development strategies.

Part of the book: Endothelial Dysfunction

By Luiza Rusu

Giant cell arteritis (GCA) is a primary systemic vasculitis characterized by systemic inflammation and vascular insufficiency of large and medium blood vessels which may lead to end-organ damage in patients age 50 and older. Standard corticosteroid treatment of GCA significantly improves the intima-media thickness while having less influence on vascular endothelial dysfunction. GCA morbidity may be related to both cardiovascular complications and corticosteroid toxicity. Therefore, we aim to discuss 1) characteristic aspects of vascular damage, 2) several mechanisms that cause vascular dysfunction, intima-media ‘nodular’ thickness, progressive narrowing of the arterial lumen and vascular blockage in the context of systemic inflammation, thrombosis and of the cardiovascular complications in GCA and 3) new therapeutic glucocorticosteroid-sparing (GS) agents which might be a more productive way of avoiding the invalidating or life-threatening cardiovascular complications of GCA.

Part of the book: Giant-Cell Arteritis

By Luiza Rusu

Endothelial cells produce huge proteomes from a relatively small total number of ECs. The ECs’ complex intercellular communication is possible through well-stored, classified, and compartmentalized secretory pathways, intermediated by the secretory vesicles and granules, with the purpose to maintain vascular homeostasis and integrity. Secreted proteins are involved in a myriad of cell communication processes. The local vascular microenvironment dynamically and constantly modifies the ECs’ secretome. We focus on the biological significance of secretome proteins in a healthy vascular microenvironment and under cardiovascular conditions. Vascular ECs crosstalk with other ECs, and other blood cells at a distance, with the circulating hematopoietic stem cells permitting adequate reactions to vascular injury, systemic or local inflammation, and viral or parasitic infections. Here, we overview current secretome biomarkers in vascular diseases, with a focus on their roles in diagnostic, prognostic, and therapeutics. Also, we highlighted some important pathological effects of exosome on cardiovascular disease. This chapter discusses current research directions characterizing vascular pathology conditioned secretomes, their regulation, and therapeutic pursuit. The overall aim of this chapter is to review current literature updates on endothelial secretome roles in endothelial homeostasis and in vascular disorders.

Part of the book: Periodontology